Estrogens-Progestins

Question 1

What is the regulatory feedback on the HPG axis?

Answer 1

Estrogen neg feedback on LH FSH, at mid cycle has pos feedback on LH FSH. Surge in LH

Question 2

Describe the biosynthetic sequence of steroidogenesis starting with cholesterol

Answer 2

Cholesterol in Theca cell converted to Pregnenolone - Progesterone - 17-OHP - Androstenedione - Testosterone -
Then Androstenedione and Testosterone travel to the Granulosa Cell and are converted to Estrone Estradiol Under stimulation of FSH

Question 3

What are the primary physiological actions of Estrogen and Progesterone?

Answer 3

Estrogen: Neg/Pos feedback, Endometrial proliferation
Metabolic: Decrease LDL, Inc HDL
Bone: antiresportive
Liver: Inc Plasma Prots
Blood: inc exp of COAGULATION FACTORS
Development of female parts
Menstrual Cycle: regulates FOLLICULAR phase

Progesterone: feedback regulation, prep for implantation, decrease uterine contrac
Metabolic: Inc LDL, inc fat deposition
Glucose: increased fasting glucose
Development of female parts
Menstrual Cycle: regulator of LUTEAL phase
Uterus Smooth muscle: dec contraction, decrease prostaglandin production, maintain relaxin secretion
Cervical glands: more viscous

Question 4

What are the MOA for synthetic and natural estrogens and progestins?

Answer 4

Estrogen:

• Natural (Estradiol):
• Synthetic (Ethinyl Estradiol, Mestranol):
• Non steroidal synthetic (Diethylstilbestrol):

Progesterone: Can use it in combination or alone (unlike estrogen)

• Nor-Compounds
• Medroxyprogesterone acetate (MPA)

Question 5

Compare efficacy of different types of hormone birth control

Answer 5

Emergency contraceptive:

• Combined - failure rate of 25%
• Progestin only (plan b) - failure rate of 12%

Question 6

What are the various routes of administration of hormonal contraceptives?

Answer 6

Oral: Combination or Progestin alone
Injection: Combination or Progestin alone
Implantable: Progestins alone
Intrauterine Device: Progestins alone
Transdermal: Combination
Vaginal Ring: Combination

Question 7

What are the adverse effects of each of the estrogen and progestin agonists?

Answer 7

Estrogen: Breast tenderness, Endometrial hyperplasia, Inc BLOOD COAGULATION;; Nausea, Cholestasis (From overactive LIVER!!), Migraine (Increased coag!!!), Ca? (endometrial and breast (invasive breast with combination therapy), bloating from loss of intravascular water

Progesterone:

• Breakthrough bleeding, change in vasc
• Impaired glucose tolerance
• Change in lipid metabolism
• Acne causing-19 Nor compounds
• Hirsutism - 19-Nor compounds

Question 8

What are the key adverse effects of hormone birth control?

Answer 8

Mild: Nausea, Mastalgia, Breakthrough bleeding (from estrogen), Edema, Headache

Moderate: Breakthrough bleeding (from progesterone), Wt gain, acne, hirsutism (adjust to less androgenic 19-nor), vaginal infections, amenorrhea

Severe: Thromboembolic disease, MI, Cerebrovascular dz, GI, Depression, Cancer

HRT - Combination therapy: Invasive Breast Cancer (likely due to progestin)
HRT - Estrogen monotherapy: Endometrial cancer
Contraceptive therapy: Reduced risk of Ovarian/Endometrial Cancer
Cancer Mechanism: trophic effect of hormones/ROS

Question 9

What are the therapeutic uses of estrogens and progestins?

Answer 9

Estrogen:
Use:
1. Hypogonadism
2. Hormone Replacement Therapy (bone dens, suppress hot flash, suppress urogenital atrophy) use less than 5 yrs
3. Contraception (suppress LH surge)
4. Acne Tx (may suppress steroidogenesis, inc SHBG production, causes less T to be developed and more to be bound in blood)

Progesterone:
Use:
1. Contraceptive: neg feedback, inc CERVICAL VISCOSITY
2. Hormone Replacement Therapy: decrease in endomet hyperplasia caused by estrogen
3. Dysmenorrhea - decrease endometrial mass - dec prostaglandin production
4. Endometriosis: inhibit proliferation of endometrial

Question 10

Compare and contrast differences in
Combination Contraceptives:
Long Acting Contraceptives:
Post Coital Contraceptives:

Answer 10

Combination Contraceptives: suppress LH/FSH surge, alter cervical mucus, alter endometrium
Long Acting Contraceptives: Implantable, IUD, Injectable (Depo-Provera),
Post Coital Contraceptives: Plan B is popular, only 12% fail rate

Question 11

Key outcomes of the Women’s Health Initiatives Studies

Answer 11

Estrogen PLUS Progesterone in healthy postmenopausal women:
INCREASED risk for: Coronary Heart disease, Stroke, Pulmonary Embolism, Invasive Breast Cancer
DECREASED risk for: Colorectal Cancer, Hip Fracture